title: A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.
abstract: BACKGROUND
  Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity.
  
  
  METHODS
  BEVLiN was an open-label, single-arm, multinational, phase II trial. Nephrectomized patients with treatment-naive, clear cell mRCC and favourable/intermediate Memorial Sloan-Kettering Cancer Center scores received bevacizumab (10 mg/kg every 2 weeks) and IFN (3 MIU thrice weekly) until disease progression. Descriptive comparisons with AVOREN patients having favourable/intermediate MSKCC scores treated with bevacizumab plus IFN (9 MIU) were made. Primary end points were grade ≥3 IFN-associated adverse events (AEs) and progression-free survival (PFS). All grade ≥3 AEs and bevacizumab/IFN-related grade 1-2 AEs occurring from first administration until 28 days after last treatment were reported.
  
  
  RESULTS
  A total of 146 patients were treated; the median follow-up was 29.4 months. Any-grade and grade ≥3 IFN-associated AEs occurred in 53.4% and 10.3% of patients, respectively. The median PFS and overall survival were 15.3 [95% confidence interval (CI): 11.7-18.0] and 30.7 months (95% CI: 25.7-not reached), respectively. The ORR was 28.8%.
  
  
  CONCLUSIONS
  Compared with a historical control AVOREN subgroup, low-dose IFN with bevacizumab resulted in a reduction in incidence rates of IFN-related AEs, without compromising efficacy [NCT00796757].
authors.affiliation: Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic. bohuslav.melichar@fnol.cz
authors.forename: B
authors.initials: B
authors.lastname: Melichar
authors.forename: S
authors.initials: S
authors.lastname: Bracarda
authors.forename: V
authors.initials: V
authors.lastname: Matveev
authors.forename: B
authors.initials: B
authors.lastname: Alekseev
authors.forename: S
authors.initials: S
authors.lastname: Ivanov
authors.forename: A
authors.initials: A
authors.lastname: Zyryanov
authors.forename: R
authors.initials: R
authors.lastname: Janciauskiene
authors.forename: E
authors.initials: E
authors.lastname: Fernebro
authors.forename: P
authors.initials: P
authors.lastname: Mulders
authors.forename: S
authors.initials: S
authors.lastname: Osborne
authors.forename: S
authors.initials: S
authors.lastname: Jethwa
authors.forename: G
authors.initials: G
authors.lastname: Mickisch
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.forename: R J A
authors.initials: RJ
authors.lastname: van Moorselaar
authors.forename: M
authors.initials: M
authors.lastname: Staehler
authors.forename: N
authors.initials: N
authors.lastname: Magne
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: VEGF; angiogenesis; bevacizumab; immunotherapy; interferon; renal cell carcinoma